This project will test the hypothesis that human polymorphonuclear leukocytes (PMNs) phagocytize, subsequently inactivate vaccinia virus, and in doing so are unable to respond to secondary phagocytic stimuli. Specifically, attempts will be made to determine if virus is engulfed by human PMNs; the role of serum complement and specific antibody in attachment, phagocytosis and possible killing; the changes in O2 metabolism associated with attachment or engulfment; if virus particles are inactivated and the killing processes employed; and if PMNs exposed to virus are able to respond to a secondary bacterial challenge. Individual and combined preparations of live and killed vaccinia virus, specific human anti-vaccinia antibody preparations, and serum complement preparations (containing alternative and classical pathway activity, complement deficient sera, or purified complement components) which elaborate chemilumescence (CL) production by human PMNs will be defined. Reactant mixtures and ratios will be utilized to examine: adherence to or engulfment by PMNs by transmission electron microscopy; oxygen radical identification; virus inactivation and degradation by whole PMNs, O2 radicals, granule constituents, antibody and complement; and CL production and killing capacity of PMNs after exposure to virus and subsequent challenge with bacteria. The data generated using these biological, chemical and immunological techniques will add to our basic knowledge of virus infections; suggest methods which will be useful for studying PMN interaction with other viruses, (i.e., influenza); and provide information regarding immune complex activation of PMNs important in understanding the pathophysiology of a number of diseases.